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We describe presenting clinical and imaging manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-associated Rhino-oculo-cerebral mucormycosis (ROCM) in a hospital setting during the second wave of SARS-CoV-2 pandemic in India. Data on the presenting manifestations were collected from 1 March to 31 May 2021. Associations between clinical and imaging findings were explored, specifically: (1) the presence or absence of orbital pain and infiltration of a superior orbital fissure on imaging; (2) the presence of unilateral facial nerve palsy and pterygopalatine fossa infiltration and geniculate ganglion signal on contrast magnetic resonance imaging, and (3) vision loss and optic nerve findings on imaging. Orbital pain was reported by 6/36 subjects. A fixed, frozen eye with proptosis and congestion was documented in 26 (72%), complete vision loss in 23 (64%), and a unilateral lower motor neuron facial nerve palsy in 18 (50%). No association was found between the presence of orbital pain and superior orbital fissure infiltration on imaging. The ipsilateral geniculate ganglion was found to enhance more profoundly in 7/11 subjects with facial palsy and available magnetic resonance (MR) imaging, and the ipsilateral pterygopalatine fossa was found infiltrated in 14. Among 23 subjects with complete loss of vision, 9 (39%) demonstrated long-segment bright signal in the posterior optic nerve on diffusion MR images. We conclude that orbital pain might be absent in SARS-CoV-2-associated ROCM. Facial nerve palsy is more common than previously appreciated and ischemic lesions of the posterior portion of the optic nerve underlie complete vision loss. [ABSTRACT FROM AUTHOR]

Background: The public interest and demand for cosmetic surgery is growing in North America. As practices continue to advertise cosmetic procedures, male consumers must also be given fair consideration in a market targeted mostly towards women.Objectives: This study investigated the advertising trends of plastic surgery clinics to assess for prevailing gender differences among online Canadian plastic surgery practice advertising.Methods: The 2021 College of Physicians and Surgeons directory for each province and territory was utilized to identify all practicing plastic surgeons. A systematic search with Google (Mountain View, CA) was conducted to analyze the websites of Canadian plastic surgery centers in the following manner: "[physician name] [province of practice]."Results: A total of 209 websites and 13,838 images were identified and analyzed. Of these images, 12,386 (90%) were female and 1452 (10%) were male patients or models. Although only 20% had a male services page, 62% of all centers offered gynecomastia procedures. The most common procedures targeting men were blepharoplasty (95%), liposuction (93%), and abdominoplasty (93%). The Prairies region had significantly fewer websites with male-only pages compared with all other Canadian regions.Conclusions: Despite the increase in cosmetic surgery procedures for males, the market for cosmetic surgery procedures targeted towards males remains insignificant. An increase in the advertising of in-demand male cosmetic procedures can allow for a broader consumer market and a subsequent increase in benefits for plastic surgeons. [ABSTRACT FROM AUTHOR]

Disasters around the world have adversely affected every aspect of life and panic-health of stranded persons is one such category. An effective and on-time evacuation from disaster-affected areas can avoid any panic-related health problems of the stranded persons. Although the nature of disasters differ in terms of how they occur, the evacuation of stranded persons faces approximately same set of issues related to the communication, time-sensitive computation and energy efficiency of the devices operated in the disaster-affected areas. In this paper, a cyber physical system (CPS) is proposed that takes into account various challenges of the disaster evacuation, so an efficient on-time and orderly evacuation of stranded panicked persons could be realized. The system employs fog-assisted mobile and UAV devices for time-sensitive computation services, data relaying and energy-aware computation. The system uses a fog-assisted two-factor energy-aware computation approach using data reduction, which enables the energy-efficient data reception and transmission (DRecTrans) operations at the fog nodes and compensates to extend the period for other functionalities. The data reduction at fog devices employs Novel Events Identification (NEI) and Principal Component Analysis (PCA) for detecting consecutive duplicate traffic and data summarization of high dimensional data, respectively. The proposed system operates in two spaces: physical and cyber. Physical space facilitates real-world data acquisition and information sharing with the concerned stakeholders (stranded persons, evacuation teams and medical professionals). The cyber space houses various data-analytics layers and comprises of two subspaces: fog and cloud. The fog space helps in providing real-time panic-health diagnostic and alert services and enables the optimized energy consumption of devices operate in disaster-affected areas, whereas the cloud space facilitates the monitoring and prediction of panic severity of the stranded persons, using a conditional probabilistic model and seasonal auto regression integrated moving average (SARIMA), respectively. Cloud space also facilitates the disaster mapping for converging the evacuation map to the actual situation of the disaster-affected area, and geographical population analysis (GPA) for the identification of the panic severity-based critical regions. The performance evaluation of the proposed CPS acknowledges its Logistic Regression-based panic-well being determination and real-time alert generation efficiency. The simulated implementation of NEI and PCA depicts the fog-assisted energy efficiency of the DRecTrans operations of the fog nodes. The performance evaluation of the proposed CPS also acknowledges the prediction efficiency of the SARIMA and disaster mapping accuracy through GPA. The proposed system also discusses a case study related to the pandemic disaster of coronavirus disease 2019 (COVID-19), where the system can help in panic-based selective testing of the persons, and preventing panic due to distressing period of COVID-19 outbreak. [ABSTRACT FROM AUTHOR]

Background ageing is an important risk factor for a variety of human pathologies. Biological age (BA) may better capture ageing-related physiological changes compared with chronological age (CA). Objective we developed a deep learning (DL) algorithm to predict BA based on retinal photographs and evaluated the performance of our new ageing marker in the risk stratification of mortality and major morbidity in general populations. Methods we first trained a DL algorithm using 129,236 retinal photographs from 40,480 participants in the Korean Health Screening study to predict the probability of age being ≥65 years ('RetiAGE') and then evaluated the ability of RetiAGE to stratify the risk of mortality and major morbidity among 56,301 participants in the UK Biobank. Cox proportional hazards model was used to estimate the hazard ratios (HRs). Results in the UK Biobank, over a 10-year follow up, 2,236 (4.0%) died; of them, 636 (28.4%) were due to cardiovascular diseases (CVDs) and 1,276 (57.1%) due to cancers. Compared with the participants in the RetiAGE first quartile, those in the RetiAGE fourth quartile had a 67% higher risk of 10-year all-cause mortality (HR = 1.67 [1.42–1.95]), a 142% higher risk of CVD mortality (HR = 2.42 [1.69–3.48]) and a 60% higher risk of cancer mortality (HR = 1.60 [1.31–1.96]), independent of CA and established ageing phenotypic biomarkers. Likewise, compared with the first quartile group, the risk of CVD and cancer events in the fourth quartile group increased by 39% (HR = 1.39 [1.14–1.69]) and 18% (HR = 1.18 [1.10–1.26]), respectively. The best discrimination ability for RetiAGE alone was found for CVD mortality (c-index = 0.70, sensitivity = 0.76, specificity = 0.55). Furthermore, adding RetiAGE increased the discrimination ability of the model beyond CA and phenotypic biomarkers (increment in c-index between 1 and 2%). Conclusions the DL-derived RetiAGE provides a novel, alternative approach to measure ageing. [ABSTRACT FROM AUTHOR]

Background Observational data suggest ceftaroline may be effective for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI), but comparative data with standard of care are limited. This analysis compares the outcomes of MRSA BSI treated with ceftaroline or daptomycin. Methods Multicenter, retrospective, observational cohort study of adult patients with MRSA BSI from 2010 to 2017. Patients treated with ≥72 hours of ceftaroline or daptomycin were included. Those clearing BSI before study drug and those with a pneumonia source were excluded. The primary outcome was composite treatment failure, defined as 30-day mortality, BSI duration ≥7 days on study drug, and 60-day MRSA BSI recurrence. Inverse probability of treatment weighted risk difference in composite failure between daptomycin and ceftaroline groups was computed and 15% noninferiority margin applied. Results Two hundred seventy patients were included; 83 ceftaroline and 187 daptomycin. Ceftaroline was noninferior to daptomycin with respect to composite failure (39% daptomycin, 32.5% ceftaroline; weighted risk difference, 7.0% [95% confidence interval, –5.0% to 19.0%]). No differences between treatment groups was observed for 30-day mortality or other secondary efficacy outcomes. Creatine phosphokinase elevation was significantly more common among daptomycin patients (5.3% vs 0%, P =.034). Rash was significantly more common among ceftaroline patients (10.8 vs 1.1%, P =.001). Conclusions No difference in treatment failure or mortality was observed between MRSA BSI treated with ceftaroline or daptomycin. These data support future study of ceftaroline as a primary MRSA BSI treatment and current use of ceftaroline when an alternative to vancomycin and daptomycin is required. [ABSTRACT FROM AUTHOR]

The past five decades have witnessed the unprecedented contribution of arboviral diseases towards global morbidity and disability. It is primarily attributed due to unplanned urbanization, population explosion and globalization. Out of these, dengue is considered the most important arboviral disease because of its predominant growth in the past. The presented study explores the immense potential of Internet of things (IoT), fog and cloud computing for providing technology-based healthcare solutions for dengue virus (DENV) infection. In this paper, a hierarchical healthcare computing system for controlling DENV infection using fog–cloud-assisted IoT is proposed. This system provides a real-time remote diagnosis of DENV infection in individuals and monitors and predicts their health sensitivity during its infection period. The system uses fog computing to diagnose the DENV infection status of the individuals using |$k$| -means clustering and generates immediate diagnostic alerts to individuals, at the fog layer. Furthermore, the system uses cloud computing to monitor and predict the probabilistic health sensitivity of the DENV-infected individuals using Bayesian belief network and artificial neural network, respectively, at the cloud layer. The prediction of health sensitivity in the proposed system helps the infected individuals and healthcare agencies in determining the health vulnerability of DENV-infected individuals and preventing severe or permanent health losses in the future. The proposed system is experimentally evaluated using well-defined approaches, which conform to its validity and applicability. The results obtained from the experimental evaluations of the proposed system acknowledge the performance superiority and high efficiency of the system in delivering DENV-related healthcare services in real time. [ABSTRACT FROM AUTHOR]

Human embryonic stem (hES) cells are highly sensitive to apoptotic stimuli such as DNA damage, which allows for the rapid elimination of mutated cells during development. However, the mechanisms that maintain hES cells in the primed apoptotic state are not completely known. Key activators of apoptosis, the BH3-only proteins, are present at low levels in most cell types. In contrast, hES cells have constitutive high levels of the BH3-only protein, NOXA. We examined the importance of NOXA for enabling apoptosis in hES cells. hES cells deleted for NOXA showed remarkable protection against multiple apoptotic stimuli. NOXA was constitutively localized to the mitochondria, where it interacted with MCL1. Strikingly, inhibition of MCL1 in NOXA knockout cells was sufficient to sensitize these cells to DNA damage-induced cell death. Our study demonstrates that an essential function of constitutive high levels of NOXA in hES cells is to effectively antagonize MCL1 to permit rapid apoptosis. [ABSTRACT FROM AUTHOR]

Background. Recurrent Clostridioides difficile infections (rCDI) are a global public health threat. To reduce rCDI, microbiotarestoring therapies are needed, particularly standardized, easy-to-administer formulations. Methods. This phase I open-label trial assessed the safety, efficacy in preventing rCDI recurrence, and intestinal microbiome effects of RBX7455, a room temperature-stable, orally administered investigational live biotherapeutic. Adult participants with 1 or more prior episodes of rCDI received: 4 RBX7455 capsules twice daily for 4 days (group 1); 4 RBX7455 capsules twice daily for 2 days (group 2); or 2 RBX7455 capsules twice daily for 2 days (group 3). For all groups, the first dose was administered in clinic, with remaining doses selfadministered at home. Adverse events were monitored during and for 6 months after treatment. Treatment success was defined as rCDI prevention through 8 weeks after treatment. Participants’ microbiome composition was assessed prior to and for 6 months after treatment. Results. Nine of 10 group 1 patients (90%), 8 of 10 group 2 patients (80%), and 10 of 10 group 3 patients (100%) were recurrencefree at the 8-week endpoint with durability to 6 months. Seventy-five treatment-emergent adverse events were observed in 27 participants with no serious investigational product-related events. Prior to treatment, participants’ microbiomes were dissimilar from the RBX7455 composition with decreased Bacteroidia- and Clostridia-class bacteria, whereas after treatment, responders’ microbiomes showed increased Bacteroidia and Clostridia. Conclusions. Three dosing regimens of RBX7455 were safe and effective at preventing rCDI. Responders’ microbiomes converged toward the composition of RBX7455. These results support its continued clinical evaluation. [ABSTRACT FROM AUTHOR]

While neuro-cognitive work examining aggression has examined patients with conditions at increased risk for aggression or individuals self-reporting past aggression, little work has attempted to identify neuro-cognitive markers associated with observed/recorded aggression. The goal of the current study was to determine the extent to which aggression by youth in the first three months of residential care was associated with atypical responsiveness to threat stimuli. This functional MRI study involved 98 (68 male; mean age = 15.96 [sd = 1.52]) adolescents in residential care performing a looming threat task involving images of threatening and neutral human faces or animals that appeared to be either loom or recede. Level of aggression was negatively associated with responding to looming stimuli (irrespective of whether these were threatening or neutral) within regions including bilateral inferior frontal gyrus, right inferior parietal lobule, right superior/middle temporal gyrus and a region of right uncus proximal to the amygdala. These data indicate that aggression level is associated with a decrease in responsiveness to a basic threat cue-looming stimuli. Reduced threat responsiveness likely results in the individual being less able to represent the negative consequences that may result from engaging in aggression, thereby increasing the risk for aggressive episodes. [ABSTRACT FROM AUTHOR]

Background Fecal microbiota transplantation (FMT) is highly effective for preventing recurrent Clostridioides difficile infection (CDI). Durability (no recurrence despite additional risk factor exposure) of FMT protection is largely unknown. We studied the durability of FMT in patients with recurrent CDI. Methods We conducted a retrospective study of adults undergoing FMT for recurrent CDI. Data collected included demographics, CDI risk factors (comorbidities, healthcare exposure, non-CDI antibiotic use, acid suppressant medications), and future CDI episodes. Durable response to FMT was defined as lack of CDI episodes within 1 year post-FMT despite risk factor exposure. Results Overall, 460 patients were included (median age, 57 years [18–94]; 65.2% female). Comorbidities included chronic liver disease, 12.8% (n = 59); cancer, 11.7% (n = 54); chronic kidney disease, 3.9% (n = 18); and inflammatory bowel disease, 21.9% (n = 101). Overall, 31.3% (n = 144) received antibiotics, 21.7% (n = 100) received acid suppressants, and 76.8% (n = 350) had healthcare exposure after FMT. Of 374 patients with risk factor exposure, 78.1% (95% confidence interval [CI], 72.7%–84.0%) had durable response to FMT at 1 year. On multivariable analysis, antibiotic use was independently associated with decreased durability of FMT (hazard ratio, 0.27; 95% CI,.15–.49; P  < .001). Conclusions The majority of patients had a durable response to FMT despite exposure to CDI risk factors. Antibiotic exposure after FMT independently predicted loss of durability of FMT. Larger studies are needed to define predictors of durable response in patients with and without exposure to antibiotics. [ABSTRACT FROM AUTHOR]

Background Recurrent Clostridioides difficile infection (rCDI) is associated with loss of microbial diversity and microbe-derived secondary bile acids, which inhibit C. difficile germination and growth. SER-109, an investigational microbiome drug of donor-derived, purified spores, reduced recurrence in a dose-ranging, phase (P) 1 study in subjects with multiple rCDIs. Methods In a P2 double-blind trial, subjects with clinical resolution on standard-of-care antibiotics were stratified by age (< or ≥65 years) and randomized 2:1 to single-dose SER-109 or placebo. Subjects were diagnosed at study entry by PCR or toxin testing. Safety, C. difficile–positive diarrhea through week 8, SER-109 engraftment, and bile acid changes were assessed. Results 89 subjects enrolled (67% female; 80.9% diagnosed by PCR). rCDI rates were lower in the SER-109 arm than placebo (44.1% vs 53.3%) but did not meet statistical significance. In a preplanned analysis, rates were reduced among subjects ≥65 years (45.2% vs 80%, respectively; RR, 1.77; 95% CI, 1.11–2.81), while the <65 group showed no benefit. Early engraftment of SER-109 was associated with nonrecurrence (P <.05) and increased secondary bile acid concentrations (P <.0001). Whole-metagenomic sequencing from this study and the P1 study revealed previously unappreciated dose-dependent engraftment kinetics and confirmed an association between early engraftment and nonrecurrence. Engraftment kinetics suggest that P2 dosing was suboptimal. Adverse events were generally mild to moderate in severity. Conclusions Early SER-109 engraftment was associated with reduced CDI recurrence and favorable safety was observed. A higher dose of SER-109 and requirements for toxin testing were implemented in the current P3 trial. Clinical Trials Registration NCT02437487, https://clinicaltrials.gov/ct2/show/NCT02437487?term=SER-109&draw= 2&rank=4. [ABSTRACT FROM AUTHOR]

Introduction: Sparse data and conflicting evidence exist on the prevalence and prognosis of organophosphate (OP)-related cardiac toxicity. We aimed to characterize the cardiac abnormalities of OP after an acute cholinergic crisis in adults without previous cardiovascular conditions. Patients and Methods: We did a prospective observational study in a tertiary-care hospital of north India (Postgraduate Institute of Medical Education and Research, Chandigarh) in 74 patients aged =13 years admitted with acute OP poisoning after self-ingestion. A systemic evaluation, including clinical characteristics, electrocardiography, and echocardiography, was performed to estimate the prevalence and prognosis of cardiac injury. A rate-corrected QT interval was calculated using Bazett's method, and >440 milliseconds was used to define prolongation. Results: Chlorpyrifos was the most commonly ingested OP (n = 29). The patients had a similar occurrence of hypotension (n = 10) and hypertension (n = 9) at admission, and electrocardiography demonstrated sinus tachycardia in 38 (51.3%) and sinus bradycardia in one case. During the hospital stay, 3 out of 74 patients had a prolonged rate-corrected QT interval (457, 468, and 461 milliseconds), and one patient developed supraventricular tachycardia. Eight (10.8%) patients developed the intermediate syndrome, and six (8.1%) died. None of the hemodynamic or electrocardiographic abnormalities was associated with in-hospital mortality or intermediate syndrome development on univariant analysis. Baseline echocardiography at hospital discharge was performed in 27 patients (admitted during 2018) and normal in all except mild tricuspid regurgitation in one. At a 6-month follow-up, 23 cases were available for cardiovascular screening (including echocardiography) and had a normal evaluation. Conclusion: Cardiac toxicity is uncommon after acute OP self-ingestion and lacks prognostic significance. [ABSTRACT FROM AUTHOR]

Objective Sexually transmitted infections because of Neisseria gonorrhoeae (NG) and/or Chlamydia trachomatis (CT) remain a major public health problem. Although the literature describes the population-based epidemiology of CT/NG, it does not appear to contain reference points for the statistical analyses of specimen positivity rates by nucleic acid testing (NAT) with polymerase chain reaction (PCR) that would be collected by a laboratory following best laboratory and regulatory practice. For facilities that diagnose NG and CT by a real-time PCR assay, an understanding of the expected specimen positivity rate of gonorrhea and chlamydia would be helpful for monitoring the assay for quality assurance. Therefore, on behalf of the Michael J. Crescenz Veteran Affairs Medical Center (VAMC), we present this novel quality assurance study on its CT/NG specimen positivity rates conducted by NAT with PCR. Methods Quality assurance/improvement quarterly data from April 1, 2012 to September 30, 2019 were reviewed to obtain both the test volume of PCR for CT/NG and the number of positive test results at the VAMC to collate and perform statistical analyses. Testing had been performed using the Abbott m2000 RealTime System (Abbott Park, IL). Results A total of 22,709 PCR tests for CT/NG had been performed on the veteran population; of these, 502 tests were positive for NG and 744 were positive for CT. Quarterly percentage rates ranged from 1.67% to 5.30% for CT and from 1.00% to 3.25% for NG, with average rates of 3.35% and 2.22% for CT and NG, respectively. Conclusion The establishment of an expected rate of specimen positivity of CT/NG by NAT with PCR at the VAMC is a significant novel reference point in the quality assurance (QA) literature and provides a benchmark that aids tremendously in QA for the microbiology/molecular laboratory. [ABSTRACT FROM AUTHOR]

Bilateral visual impairment includes participants with visual impairment in one eye and visual impairment/blindness in the other eye. e Presence of any existing cataract or any history of cataract surgery in either eye (Modified Wisconsin Cataract Grading System). f Among diabetic individuals. g VTDR, vision-threatening diabetic retinopathy. Bilateral visual impairment includes participants with visual impairment in one eye and visual impairment/blindness in the other eye. d Based on the WHO definition, visual impairment was defined as VA<20/60 to 20/400. The overall age-adjusted BCVA prevalence of bilateral blindness (VA< 20/200, based on the better-seeing eye) and VI (VA< 20/40 to 20/200, based on the better-seeing eye) was 0.3% [95% confidence interval (CI) 0.2-0.4] and 4.2% (95% CI 3.8- 4.5), respectively. Globally, blindness and visual impairment (VI) are estimated to affect 36 million and 400 million people, respectively. [Extracted from the article]

Objective This study aimed to describe and validate a novel ultrasound-guided intercostal peripheral nerve stimulator implantation technique. Methods The fifth to tenth ribs on both sides of an unembalmed cadaveric specimen were localized using a 15–6-MHz linear array transducer, counting distally from T-1 bilaterally. A single interventionist then implanted 12 peripheral nerve stimulators on the fifth through tenth ribs, six MicroLeads on the left side and six StimRouters on the right side, using an in-plane lateral to medial approach to the inferior border of the corresponding rib. After all the stimulators were implanted, their location was confirmed using fluoroscopy. Gross anatomic dissection was later performed for each of the stimulators placed, and the distance of the lead from the intercostal nerve and pleura was noted. Results All leads were noted in an accurate position in the plane between the inner and innermost intercostal muscle, without any intrapleural placement. The distance of the leads from the intercostal nerves was on average 2.3 mm and 1.1 mm for MicroLead and StimRouter, respectively. Conclusions To our knowledge, this study is the first to determine the feasibility of ultrasound-guided peripheral nerve stimulator placement in close proximity to the pleura. All the stimulator leads were accurately placed using our ultrasound-guided technique and were within 0.5–3 mm from the intercostal nerve. Although this technique might prove technically challenging, the use of ultrasound for intercostal peripheral nerve stimulator implantation appears feasible and warrants further investigation to establish this as an acceptable technique for patients. [ABSTRACT FROM AUTHOR]

Background Mounting evidence suggests the addition of a β-lactam (BL) to daptomycin (DAP) results in synergistic in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA) and bolsters the innate immune response to infection. This study's objective was to provide clinical translation to these experimental data and determine if DAP+BL combination therapy results in improved clinical outcomes compared with treatment with DAP alone in patients with MRSA bloodstream infections (BSIs). Methods This was a retrospective, comparative cohort study conducted at 2 academic medical centers between 2008 and 2018. Adults with MRSA BSI treated with DAP for ≥72 hours and initiated ≤5 days of culture collection were included. Patients who received a BL for ≥24 hours and initiated ≤24 hours of DAP comprised the DAP+BL group. The primary outcome was composite clinical failure (60-day all-cause mortality and/or 60-day recurrence). Analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW). Results A total of 229 patients were included (72 DAP+BL and 157 DAP). In unadjusted and IPTW-adjusted analyses, DAP+BL was associated with significantly reduced odds of clinical failure (odds ratio [OR], 0.362; 95% confidence interval [CI],.164–.801; adjusted OR, 0.386; 95% CI,.175–.853). Adjusted analyses restricted to prespecified subgroups based on infection complexity and baseline health status were consistent with the main analysis. Conclusions The addition of a BL to DAP was associated with improved clinical outcomes in patients with MRSA BSI. This study provides support to ongoing and future studies evaluating the impact of combination therapy for invasive MRSA infections. Patients treated with daptomycin plus a β-lactam for MRSA bloodstream infection had lower odds of composite clinical failure defined as 60-day all-cause mortality and/or 60-day recurrence compared with patients treated with daptomycin monotherapy after adjusting for confounding variables using inverse probability of treatment weighting. [ABSTRACT FROM AUTHOR]

Introduction: In patients with prior myocardial infarction (MI), cardiac rehabilitation (CR) has been shown to reduce all-cause mortality, cardiac mortality, and risk of recurrent MI. Medically supervised cardiac rehab has challenges such as increased patient and center cost, patient transportation issues, patient time commitment, and increased need for resources. Home-based cardiac rehabilitation (HBCR) is an innovative alternative to medically supervised CR which can help to address some of the aforementioned issues. HBCR has been shown to have similar patient outcomes when compared to medically supervised CR; however, implantation efforts and experiences within Veteran Affair (VA) facilities were limited. Thus, we sought to describe our implementation efforts and outcomes of HBCR at our VA medical center, since our VA medical center does not offer an on-site medically supervised CR program.Materials and Methods: The project was not reviewed by our institutional review board as this quality improvement project was determined by our VA medical service chief to not qualify as human subjects research. Veterans eligible for CR in our VA medical system were enrolled in a 12-week HBCR program. Veterans performed exercise training at home with equipment provided at no cost. In addition, participating veterans received nutrition counseling, smoking cessation encouragement, stress management, and psychosocial consultation through weekly telephone calls performed by registered nurses. Progress was measured using Life's Simple 7, Duke Activity status index, 6-minute walk test, and Short Form Health Survey (SF-36) before and after HBCR. Medical records were monitored for death, MI, and readmission to the hospital for CHF within the VA medical system for 1 year after the program was complete. SAS and R were used for data input and analysis.Results: Data from 213 veterans were available for analysis and 136 of these veterans completed the HBCR program; the 95 veterans who did not complete the program either declined enrollment, discontinued follow-up with this program, or failed to actively participate and thus were removed from the program. Veterans who completed the 12-week HBCR program reported significant improvement, when compared before and after HBCR program, in Simple 7, Duke Activity status index metabolic equivalent of tasks, 6-minute walk test, SF-36 physical functioning, SF-36 bodily pain, and SF-36 vitality. Overall survival and recurrent MIs were similar between the veterans who completed and the veterans who did not complete the HBCR program in the 1 year follow-up. Hospital admission for heart failure in the 1-year follow-up was lower among veterans who completed the HBCR program when compared to the veterans who did not complete the HBCR program.Conclusions: HBCR is an effective alternative to facility-based CR. Veterans who completed the program showed improvement in physical capacity and functional status. Compared to those who were eligible but did not complete the program, hospitalization for heart failure was reduced after completing HBCR. [ABSTRACT FROM AUTHOR]

Motivation Despite conservation in general architecture of promoters and protein–DNA interaction interface of RNA polymerases among various prokaryotes, identification of promoter regions in the whole genome sequences remains a daunting challenge. The available tools for promoter prediction do not seem to address the problem satisfactorily, apparently because the biochemical nature of promoter signals is yet to be understood fully. Using 28 structural and 3 energetic parameters, we found that prokaryotic promoter regions have a unique structural and energy state, quite distinct from that of coding regions and the information for this signature state is in-built in their sequences. We developed a novel promoter prediction tool from these 31 parameters using various statistical techniques. Results Here, we introduce SEProm, a novel tool that is developed by studying and utilizing the in-built structural and energy information of DNA sequences, which is applicable to all prokaryotes including archaea. Compared to five most recent, diverged and current best available tools, SEProm performs much better, predicting promoters with an ' F -value' of 82.04 and 'Precision' of 81.08. The next best ' F -value' was obtained with PromPredict (72.14) followed by BProm (68.37). On the basis of 'Precision' value, the next best 'Precision' was observed for Pepper (75.39) followed by PromPredict (72.01). SEProm maintained the lead even when comparison was done on two test organisms (not involved in training for SEProm). Availability and implementation The software is freely available with easy to follow instructions (www.scfbio-iitd.res.in/software/TSS%5fPredict.jsp). Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Background Fecal microbiota transplantation (FMT) is highly effective for treating recurrent Clostridium difficile infection (CDI) in observational studies (>90%), but cure rates in clinical trials are lower. We performed a systematic review and meta-analysis to assess the efficacy of FMT for recurrent CDI in open-label studies and clinical trials. Methods A systematic search from January 1978 to March 2017 was performed to include clinical trials of FMT for CDI. We analyzed CDI resolution by calculating weighted pooled rates (WPRs). Results Thirteen trials were included, comprising 610 patients with CDI treated with single FMT. Overall, 439 patients had clinical cure (WPR, 76.1%; 95% confidence interval (CI), 66.4%–85.7%). There was significant heterogeneity among studies (I 2 = 91.35%). Cure rates were lower in randomized trials (139/216 patients; WPR, 67.7%; 95% CI, 54.2%–81.3%) than in open-label studies (300/394 patients; WPR, 82.7%; 71.1%–94.3%) (P <.001). Subgroup analysis by FMT delivery modality showed lower cure rates with enema than colonoscopy (WPR, 66.3% vs 87.4%; P <.001) but no difference between colonoscopy and oral delivery (WPR, 87.4% vs 81.4%; P =.17). Lower rates were seen for studies including both recurrent and refractory CDI than for those including only recurrent CDI (WPR, 63.9% vs 79%; P <.001). Conclusions FMT was associated with lower cure rates in randomized trials than in open-label and in observational studies. Colonoscopy and oral route are more effective than enema for stool delivery. The efficacy also seems to be higher for recurrent than for refractory CDI. [ABSTRACT FROM AUTHOR]

Background: Published guidelines call for prolonged courses of intravenous (iv) antibiotics for the treatment of MRSA bloodstream infection (BSI) to ensure eradication of deep foci and decrease relapse risk. Sequential iv-to-oral antibiotic therapy has been successfully applied to other serious infections but has not been evaluated for MRSA BSI.Objectives: To compare outcomes in adults completing MRSA BSI therapy with oral versus parenteral antibiotics in the outpatient setting [oral outpatient antibiotic therapy (OOAT) versus outpatient parenteral antibiotic therapy (OPAT)].Methods: This was a single-centre, retrospective, cohort study between 2008 and 2018. The primary outcome was 90 day clinical failure (MRSA BSI recurrence, deep-seated MRSA infection or all-cause mortality). Analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW).Results: A total of 492 patients were included (70 OOAT, 422 OPAT). In general, OOAT patients had characteristics consistent with a lower risk of poor outcomes; however, after IPTW key prognostic factors were balanced. In IPTW-adjusted analysis, there was non-significant reduction in the rate of 90 day clinical failure in the OOAT group compared with the OPAT group [adjusted HR (aHR) 0.379, 95% CI 0.131-1.101]. In analyses restricted to pre-specified subgroups defined by index infection complexity and comorbidity burden, findings were consistent with the main analysis. Furthermore, OOAT patients had a significantly reduced rate of 90 day hospital readmission (aHR 0.603, 95% CI 0.388-0.937).Conclusions: We provide preliminary evidence that selected patients with MRSA BSI may have at least equivalent clinical outcomes with OOAT versus OPAT and provide support to ongoing and future studies evaluating oral antibiotics for MRSA BSI. [ABSTRACT FROM AUTHOR]

Background Visual impairment in developing countries has both social and economic impact on individuals and communities. Understanding the subjective visual functioning of populations will allow for local policymakers to identify the need for optometric or ophthalmic services in their communities. Methods The authors surveyed 644 adult patients in Mwanza, Tanzania at three clinics (Buzuruga, Mwananchi and Kisesa) using a modified Visual Functioning Questionnaire 25. Responses were categorized into General health, General vision, Ocular pain, Near activities, Distance activities, Social function, Mental health, Role difficulties, Color vision, Peripheral vision and Dependency. Results Patients at Buzuruga reported the lowest scores on most subscales. Of 100 employed patients, 37% claimed to have at least some difficulty in performing job duties due to their eyesight. At Kisesa, 146 (246/221) patients (66.1%) had never had an eye exam, compared with 134/227 (59.0%) at Buzuruga and 69/173 (39.9%) at Mwananchi (p<0.01). Common reasons for not seeing an eye doctor were the perceived expense and lack of vision problems. Conclusions Due to regional differences in visual functioning in Mwanza, a national effort for vision health cannot be entirely successful without addressing the individualized needs of local communities. Reducing the cost of vision care appointments may expand vision health care utilization in Mwanza. [ABSTRACT FROM AUTHOR]

Background Despite advancements, recurrent Clostridium difficile infections (CDI) remain an urgent public health threat with insufficient response rates to currently approved antibiotic therapies. Microbiota-based treatments appear effective, but rigorous clinical trials are required to optimize dosing strategies and substantiate long-term safety. Methods This randomized, double-blind, placebo-controlled phase 2B trial enrolled adults with 2 or more CDI recurrences to receive: 2 doses of RBX2660, a standardized microbiota-based drug (group A); 2doses of placebo (group B); or 1 dose of RBX2660 followed by 1 dose of placebo (group C). Efficacy was defined as prevention of recurrent CDI for 8 weeks following treatment. Participants who had a recurrence within 8 weeks were eligible to receive up to 2 open-label RBX2660 doses. The primary endpoint was efficacy for group A compared to group B. Secondary endpoints included the efficacy of group C compared to group B, combined efficacy in the blinded and open-label phases, and safety for 24 months. Results The efficacy for groups A, B, and C were 61%, 45%, and 67%, respectively. The primary endpoint was not met (P =.152). One RBX2660 dose (group C) was superior to placebo (group B; P =.048), and the overall efficacy (including open-label response) for RBX2660-treated participants was 88.8%. Adverse events did not differ significantly among treatment groups. Conclusions One, but not 2, doses of RBX2660 was superior to placebo in this randomized, placebo-controlled trial. These data provide important insights for a larger phase 3 trial and continued clinical development of RBX2660. Clinical Trials Registration NCT02299570. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study is to evaluate the development of a 1-wk screening campaign and efforts towards the implementation of a sustainable system that addresses cervical cancer in Mwanza, Tanzania with a screen-and-treat model utilizing visual inspection of the cervix with acetic acid (VIA) and cryotherapy. Methods: In partnership with CureCervicalCancer (CCC), a non-profit organization based in Los Angeles, CA, USA, 11 medical students at the University of California, Irvine School of Medicine established a model for sustainable human papillomavirus screening practices in Mwanza, Tanzania. This study both quantitatively and qualitatively assesses the successes and limitations of the program model. Results: During the 5-day training, a total of 614 women attended the screenings and 556 women were screened with VIA, of whom 10.6% (n=59) were VIA positive and 89.4% (n=499) were VIA negative. Of those who were VIA positive, 83.1% (n=49) received cryotherapy while 16.9% (n=10) did not due to suspicion of advanced cancer (n=7), refusal to receive cryotherapy (n=2) or pregnancy (n=1). Conclusions: The screen-and-treat model for the identification and treatment of precancerous cervical lesions is an effective public health intervention with the potential to impact women by providing the tools and education needed by local healthcare professionals. However, limitations common to resource-poor settings, such as continuity of funding, loss to follow-up and transportation costs, remain barriers to sustainability. [ABSTRACT FROM AUTHOR]

Abstract: The brief lifespan of the polymorphonuclear neutrophil (PMN) is regulated through its capacity to undergo apoptosis, a constitutive process that is actively inhibited during sepsis. We sought to define the cellular mechanisms through which Heat Shock Protein 90 (Hsp90) prolongs the survival of inflammatory PMN. We evaluated Hsp90 expression and interaction with client proteins in PMNs from patients with sepsis and in healthy control PMNs treated with LPS (1 μg/mL). Hsp90 activity was inhibited pharmacologically using radicicol (Rad; 1 μM), and Hsp90 transcription was silenced in septic PMN using siRNA. PMN apoptosis was evaluated by flow cytometry and expression of cleaved caspase‐8 and ‐3. Septic PMNs showed reduced rates of apoptosis compared with control PMNs 21 h after isolation, and Hsp90‐α mRNA was significantly more abundant in septic PMN. Caspase‐8 coimmunoprecipitated with Hsp90, c‐Src, and the p85 inhibitory subunit of PI3K in both septic and LPS‐treated PMN. Inhibition of Hsp90 activity with Rad or its translation using siRNA restored basal rates of apoptosis in both septic and LPS‐treated PMN. Radicicol further reduced c‐Src protein abundance, increased the ubiquitination of caspase‐8 and c‐Src, and enhanced the cleavage of caspase‐8 and ‐3. We conclude that Hsp90 prolongs the survival of activated neutrophils by stabilizing a molecular complex of c‐Src kinase and caspase‐8, preventing their ubiquitination, and resulting in inhibition of the catalytic activity of caspase‐8 and ‐3. [ABSTRACT FROM AUTHOR]

Background. The choice of antibiotics for systemic infections in patients with a high risk of Clostridium difficile infection (CDI) remains a clinical practice dilemma. Although some studies suggest that tetracyclines may be associated with a lower risk of CDI than other antibiotics, other results are conflicting. We conducted a systematic review and metaanalysis of studies that assessed the risk of CDI with tetracyclines compared to other antibiotics. Methods. We conducted a systematic search of Medline, Embase, and Web of Science from January 1978 through December 2016 to include studies that assessed the association between tetracycline use and risk of CDI. Weighted summary estimates were calculated using generalized inverse variance with a random-effects model using RevMan 5.3. Study quality was assessed using the Newcastle-Ottawa scale. Results. Six studies (4 case control, 2 cohort) with patient recruitment between 1993 and 2012 were included. Metaanalysis using a random-effects model, demonstrated that tetracyclines were associated with a decreased risk of CDI (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.47-0.81; P < .001). There was significant heterogeneity, with an I2 of 53% with no publication bias. Subgroup analysis of studies that evaluated the risk of CDI with doxycycline alone also demonstrated a decreased risk of CDI (OR, 0.55; 95% CI, 0.40-0.75; P < .001). Conclusions. Metaanalyses of existing studies suggest that tetracyclines may be associated with a decreased risk of CDI compared with other antimicrobials. It may be reasonable to use tetracyclines whenever appropriate to decrease CDI associated with antibiotic use. [ABSTRACT FROM AUTHOR]

BACKGROUND There are no comprehensive guidelines on management of hypertensive emergency (HTNE) and complications. Despite advances in antihypertensive medications HTNE is accompanied with significant morbidity and mortality. METHODS We queried the 2002-2012 nationwide inpatient sample database to identify patients with HTNE. Trends in incidence of HTNE and in-hospital mortality were analyzed. Logistic regression analysis was used to assess the relationship between end-organ complications and in-hospital mortality. RESULTS Between 2002 and 2012, 129,914 admissions were included. Six hundred and thirty (0.48%) patients died during their hospital stay. There was an increase in the number of HTNE admissions (9,511-15,479; Ptrend < 0.001) with concurrent reduction of in-hospital mortality (0.8-0.3%; Ptrend < 0.001) by the year 2012 compared to 2002. Patients who died during hospitalization were older, had longer length of stay, higher cost of stay, more comorbidities, and higher risk scores. Presence of acute cardiorespiratory failure [adjusted odds ratio (OR), 15.8; 95% confidence interval (CI), 13.2-18.9], stroke or transient ischemia attack (TIA) (adjusted OR, 7.9; 95% CI, 6.3-9.9), chest pain (adjusted OR, 5.9; 95% CI, 4.4-7.7), stroke/TIA (adjusted OR, 5.9; 95% CI, 4.5-7.7), and aortic dissection (adjusted OR, 5.9; 95% CI, 2.8-12.4) were most predictive of higher in-hospital mortality in addition to factors such as age, aortic dissection, acute myocardial infarction, acute renal failure, and presence of neurological symptoms. CONCLUSION A rising trend in hospitalization for HTNE, with an overall decrease in in-hospital mortality was observed from 2002 to 2012, possibly related to changes in coding practices and improved management. Presence of acute cardiorespiratory failure, stroke/TIA, chest pain, and aortic dissection were most predictive of higher hospital mortality. [ABSTRACT FROM AUTHOR]